Nearly half of the tobacco consumed in the United States is smoked by people with psychiatric illness. In particular, smokers with schizophrenia (SWS) infrequently attempt and attain sustained smoking abstinence and have a 25-year shorter lifespan due to smoking-related illness. SWS are in dire need of effective smoking treatment and are not benefiting from treatments that are currently available. Reducing the nicotine content of cigarettes to non-addicting levels is an innovative strategy that has the potential to significantly reduce tobacco-related morbidity and mortality in this population. In evaluating the potential impact of this strategy, one critical knowledge gap that was identified is whether this strategy would be effective in smokers with serious mental illness, who are more nicotine-dependent than other smokers and who may smoke for self-medication purposes. We are currently studying the acute effects of VLNC cigarettes in SWS, with promising results showing that use of these cigarettes reverses abstinence-induced cigarette craving, withdrawal-related negative mood and usual-brand smoking. Furthermore, SWS rate the subjective effects VLNC cigarettes highly, indicating that such an approach may be acceptable to SWS. However, the effects of prolonged use of VLNC cigarettes on smoking tiehavior, psychiatric symptoms and cognitive functioning in SWS are unknown. This study would be the first to examine whether a regulatory approach of reducing the nicotine content of cigarettes to non-addicting levels is a viable method of reducing smoking in this population. Smokers will be randomized to one of two experimental conditions: 1) very low nicotine content (VLNC) cigarettes with a 0.06 mg nicotine yield (actual dose to be determined by Project 1; n = 40), or 2) normal nicotine content cigarettes (n = 40). Over the 2-week baseline and 6-week treatment phases, subjects will be assessed for patterns of tobacco use, biomarkers of exposure, subjective responses (e.g., satisfaction, craving, withdrawal symptoms), psychiatric symptoms, cognitive performance, smoking cue reactivity and smoking topography. At the end of the 6-week treatment period, subjective and behavioral responses to smoking abstinence will be assessed. The results from this study will describe the possible risks and benefits to smokers with schizophrenia of dramatically reducing the nicotine content of cigarettes. This project will complement and use similar measures as Projects 1 and 2. RELEVANCE (See instructions); There is an unusually high rate of cigarette smoking and correspondingly high rates of smoking-related morbidity and mortality in smokers with schizophrenia. This project will investigate the effects of 6-week use of very low nicotine content cigarettes on smoking, mood, psychiatric symptoms, cognitive functioning and other measures in smokers with schizophrenia. This information will help to determine whether a public health policy of limiting the nicotine content of cigarettes to very low levels would be effective and safe for these smokers